Epimedium koreanum Nakai attenuates glucocorticoid-induced osteoporosis by suppressing ferroptosis via the KEAP1/NRF2/SLC7A11/GPX4 axis: comparative pharmacodynamic evaluation of four epimedium species and proteomic and metabolomic analyses of epk
4 affiliations
- 1Innovation Practice Center, Changchun University of Chinese Medicine
- 2School of Pharmacy, Changchun University of Chinese Medicine
- 3Institute of Medicine and Drug Research, Qiqihar Medical University
- 4Scientific Research Department, Changchun University of Chinese Medicine
Abstract
Objective: The pharmacodynamics and underlying mechanisms of Epimedium (Yingyanghuo), a traditional Chinese medicine, were investigated in the context of glucocorticoid-induced osteoporosis (GIOP) management, with particular emphasis on ferroptosis inhibition. Methods: A rat model of GIOP was developed through dexamethasone (DEX) administration. Animals received extracts of the four Epimedium species; Epimedium koreanum Nakai (Epk) was selected for subsequent investigation owing to its superior preliminary efficacy. Evaluations encompassed bone microstructure, osteoclast activity, serum biomarkers of bone metabolism, oxidative stress, lipid peroxidation and iron accumulation indicators (4-HNE and Fe ²⁺ ), and ferroptosis-associated proteins (KEAP1/NRF2/SLC7A11/GPX4 pathway). Integration of proteomics and metabolomics facilitated the identification of key pathways, followed by experimental validation of ferroptosis modulation. Results: Epk treatment mitigated DEX-induced bone loss, improved bone microarchitecture, and suppressed osteoclast activity. Multi-omics approaches uncovered reversal of 368 proteins and 127 metabolites in GIOP rats following Epk administration, with enrichment observed in ferroptosis, glutathione metabolism, and oxidative phosphorylation. Treatment with Epk further reduced the elevated femoral 4-HNE and Fe ²⁺ levels in GIOP rats. Epk treatment elevated NRF2, HO-1, SLC7A11, and GPX4 and reduced KEAP1 and P53 in bone tissue, consistent with suppression of ferroptosis-related signaling. Conclusion: Epimedium, with Epk as the prominent representative, confers substantial protection against GIOP, with effects associated with modulation of the KEAP1/NRF2/SLC7A11/GPX4 pathway and suppression of ferroptosis-related markers in bone tissue, thereby providing a basis for further investigation of its clinical potential in GIOP management.
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BibTeX
@article{xu2026epimedium,
title = {{Epimedium koreanum Nakai attenuates glucocorticoid-induced osteoporosis by suppressing ferroptosis via the KEAP1/NRF2/SLC7A11/GPX4 axis: comparative pharmacodynamic evaluation of four epimedium species and proteomic and metabolomic analyses of epk}},
author = {Tian-Yang Xu and Pan Li and Zi-Meng Qi and Jing-Zhen Wu and Shi-Chang Li and Jin-Ling Liang and Jia Liu and Peng Yu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1948777},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1948777/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Epimedium koreanum Nakai attenuates glucocorticoid-induced osteoporosis by suppressing ferroptosis via the KEAP1/NRF2/SLC7A11/GPX4 axis: comparative pharmacodynamic evaluation of four epimedium species and proteomic and metabolomic analyses of epk
AU - Tian-Yang Xu
AU - Pan Li
AU - Zi-Meng Qi
AU - Jing-Zhen Wu
AU - Shi-Chang Li
AU - Jin-Ling Liang
AU - Jia Liu
AU - Peng Yu
PY - 2026
DA - 2026/10/29
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1948777
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1948777/full
AB - Objective: The pharmacodynamics and underlying mechanisms of Epimedium (Yingyanghuo), a traditional Chinese medicine, were investigated in the context of glucocorticoid-induced osteoporosis (GIOP) management, with particular emphasis on ferroptosis inhibition. Methods: A rat model of GIOP was developed through dexamethasone (DEX) administration. Animals received extracts of the four Epimedium species; Epimedium koreanum Nakai (Epk) was selected for subsequent investigation owing to its superior preliminary efficacy. Evaluations encompassed bone microstructure, osteoclast activity, serum biomarkers of bone metabolism, oxidative stress, lipid peroxidation and iron accumulation indicators (4-HNE and Fe ²⁺ ), and ferroptosis-associated proteins (KEAP1/NRF2/SLC7A11/GPX4 pathway). Integration of proteomics and metabolomics facilitated the identification of key pathways, followed by experimental validation of ferroptosis modulation. Results: Epk treatment mitigated DEX-induced bone loss, improved bone microarchitecture, and suppressed osteoclast activity. Multi-omics approaches uncovered reversal of 368 proteins and 127 metabolites in GIOP rats following Epk administration, with enrichment observed in ferroptosis, glutathione metabolism, and oxidative phosphorylation. Treatment with Epk further reduced the elevated femoral 4-HNE and Fe ²⁺ levels in GIOP rats. Epk treatment elevated NRF2, HO-1, SLC7A11, and GPX4 and reduced KEAP1 and P53 in bone tissue, consistent with suppression of ferroptosis-related signaling. Conclusion: Epimedium, with Epk as the prominent representative, confers substantial protection against GIOP, with effects associated with modulation of the KEAP1/NRF2/SLC7A11/GPX4 pathway and suppression of ferroptosis-related markers in bone tissue, thereby providing a basis for further investigation of its clinical potential in GIOP management.
SN - 1663-9812
ER -